CN113087017A - Sodium metavanadate nanosphere and preparation method and application thereof - Google Patents
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Abstract
The invention discloses a sodium metavanadate nanosphere and a preparation method and application thereof, wherein the sodium metavanadate nanosphere consists of a polymer vesicle and sodium metavanadate coated by the polymer vesicle; the polymersome is formed by water-oil amphiphilic polymer. The sodium metavanadate nanosphere can deliver sodium metavanadate to a tumor part, external stimulation is not needed, the sodium metavanadate can be released as required, the released sodium metavanadate can generate chemical kinetic reaction with hydrogen peroxide over-expressed in a tumor microenvironment to generate two active oxygen species of singlet oxygen and hydroxyl free radicals, and therefore efficient chemical kinetic treatment is achieved.
Description
Technical Field
The invention relates to the technical field of new biomedical materials. More particularly, relates to sodium metavanadate nanospheres and a preparation method and application thereof.
Background
Cancer has been one of the malignant diseases threatening human health. Conventional treatment regimens include chemotherapy, radiation therapy and surgical treatment. The drugs taken by chemotherapy, such as paclitaxel, doxorubicin hydrochloride and the like, are systemically administered, have poor targeting effect and great damage to normal cells of the whole body; radiotherapy is a local treatment method for treating tumors by using radioactive rays, and the radioactive rays can kill cancer cells and simultaneously cause great damage to normal cells.
In the biomedical field, the occurrence and development of malignant tumors create unique microenvironment, such as weak acidity and H2O2Over-expression, low catalase activity, oxygen deficiency and the like, the special microenvironment not only provides a proper growth condition for the tumor, but also enhances the invasiveness and the metastasis of the tumor, is a specific microenvironment different from normal tissues of the tumor tissue, and provides possibility for efficient and selective treatment of the tumor. The recently developed chemokinetic therapy (CDT) is defined as the over-expressed H in the weakly acidic condition of the microenvironment of tumor focus area2O2Taking the transition metal nano material as a catalyst, and initiating a chemical kinetic reaction (Fenton/Fenton-like reaction) in tumor cells in situ to catalyze H2O2Generating active species with strong oxidizing property such as OH, and inducing tumor cell apoptosis. While in normal tissue in weak alkaline conditions and small amounts of H2O2The reaction can not be carried out under the environment of (2), thereby ensuring the safety of the reaction to normal tissues. Compared with chemotherapy, radiotherapy, photothermal therapy and photodynamic therapy, CDT has better tumor specificity and selectivity and low toxic and side effects on the whole body; the treatment process does not need external field excitation, has low requirements on equipment and low treatment cost.
Although the chemokinetic therapy is rapidly developed, the therapeutic effect is still to be improved. Currently, the research for improving the effect of chemokinetic treatment is mostly based on the improvement of fenton's chemical reaction. The following four types can be roughly classified: 1. selecting a nano material with better performance to enable the nano material to have higher-efficiency Fenton reaction or Fenton-like reaction capability; 2. adjusting the reaction environment; 3. adding external energy field stimulation; 4. in combination with other treatment modalities. Therefore, the research on new chemical kinetics reaction is still blank at present, so that the development of new and efficient chemical kinetics reaction has important significance for improving the chemical kinetics treatment effect, and therefore, the sodium metavanadate nanosphere and the preparation method and the application thereof are provided.
Disclosure of Invention
The first object of the invention is to provide sodium metavanadate nanospheres. The sodium metavanadate nanosphere can be enriched on a tumor part through a high-permeability long-retention (EPR) effect, and can release sodium metavanadate under the stimulation of physiological conditions of tumors, and the sodium metavanadate can generate a new chemical kinetic reaction with hydrogen peroxide over-expressed on the tumor part to generate two strong-oxidative active species, namely hydroxyl radicals and singlet oxygen, so that the high-efficiency chemical kinetic treatment is more suitable for a tumor microenvironment.
The second purpose of the invention is to provide a preparation method of sodium metavanadate nanospheres.
The third purpose of the invention is to provide an application of the sodium metavanadate nanosphere.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a sodium metavanadate nanosphere, which is composed of a polymer vesicle and sodium metavanadate coated by the polymer vesicle; the polymersome is formed by water-oil amphiphilic polymer.
Further, the average particle size of the sodium metavanadate nanospheres is 100nm-250 nm.
Further, the water-oil amphiphilic polymer is an amphiphilic block polymer or an amphiphilic polymer comprising phospholipid and a hydrophilic polymer chain segment; the amphiphilic block polymer consists of a hydrophilic polymer chain segment and a hydrophobic polymer chain segment.
Further, when the water-oil amphiphilic polymer is an amphiphilic block polymer, the molecular weight of the hydrophilic polymer segment is 2000-5000, and the molecular weight of the hydrophobic polymer segment is 2000-5000; when the water-oil amphiphilic polymer is an amphiphilic polymer comprising phospholipids and hydrophilic polymer segments, the molecular weight of the hydrophilic polymer segments is 2000-5000.
The invention finds that the molecular weight of the water-oil amphiphilic polymer can influence the final particle size of the sodium metavanadate nanosphere; the particle size range of the invention can better realize passive targeting of the tumor, otherwise, if the particle size of the sodium vanadate nanospheres is not in the range of the invention, the aggregation of the sodium vanadate nanospheres at the tumor site can be influenced.
Preferably, the amphiphilic polymer comprising phospholipids and hydrophilic polymer segments is selected from distearoylphosphatidylacetamide-polyethylene glycol (DSPE-mPEG) and/or distearoylphosphatidylethanolamine-polyethylene glycol-folic acid (DSPE-mPEG-FA); the amphiphilic block polymer is selected from poly (lactide-co-glycolide) -polyethylene glycol (PLGA-mPEG).
In a second aspect, the invention provides a preparation method of sodium metavanadate nanospheres, which comprises the following steps:
1) dissolving the water-oil amphiphilic polymer in an organic solvent to obtain a mixed solution A;
2) dissolving sodium metavanadate in a polyvinyl alcohol aqueous solution to obtain a mixed solution B;
3) mixing the mixed solution A and the mixed solution B, and carrying out primary emulsification to obtain primary emulsion;
4) adding a polyvinyl alcohol (PVA) aqueous solution into the primary emulsion for secondary emulsification to obtain a secondary emulsion;
5) homogenizing the secondary emulsion, removing organic solvent, and concentrating.
The operation sequence of the step 1) and the step 2) is not specifically limited, and the step 1) may be performed first and then the step 2) may be performed, or the step 2) may be performed first and then the step 1) may be performed.
Further, in the method, the mass ratio of the water-oil amphiphilic polymer to the sodium metavanadate is 7-9: 2.
In the step 3), the volume ratio of the mixed solution B to the mixed solution A is 1: 4-5.
In the step 1), the organic solvent is dichloromethane or trichloromethane.
In the step 2), the solubility of the polyvinyl alcohol aqueous solution is 1mg/ml-10 mg/ml.
In the step 4), the solubility of the polyvinyl alcohol aqueous solution is 2mg/ml-20 mg/ml.
The primary emulsification and the secondary emulsification are carried out in an ultrasonic crusher; preferably, the parameters of the ultrasonicator are as follows: the size of the amplitude transformer is 6-10 mm; the power is 200-400W; the ultrasonic time is 1-3s, and the gap time is 1-2 s.
The invention discovers that the emulsification process can influence the final structure of the sodium metavanadate nanosphere, and if the primary emulsification and the secondary emulsification are not carried out in the ultrasonic crusher with the specific parameter range, the sodium metavanadate nanosphere can not be obtained.
In a third aspect, the invention provides an application of sodium metavanadate nanospheres in preparation of a medicament or a reagent for chemokinetic treatment.
Preferably, the sodium metavanadate nanosphere is applied to preparation of a drug or a reagent for treating tumors through chemokinetics.
It is noted that any range recited herein includes the endpoints and any values therebetween and any subranges therebetween with the endpoints or any values therebetween, unless otherwise specified. The preparation method in the invention is a conventional method unless otherwise specified, and the raw materials used are commercially available from public sources or prepared according to the prior art unless otherwise specified, the percentages are mass percentages unless otherwise specified, and the solutions are aqueous solutions unless otherwise specified.
The invention has the advantages of
1. The sodium metavanadate nanosphere provided by the invention can be enriched on a tumor part through a high permeation and long retention (EPR) effect, can release sodium metavanadate under the stimulation of a tumor physiological condition, can generate a new chemical kinetic reaction with hydrogen peroxide over-expressed on the tumor part, can generate hydroxyl radicals and singlet oxygen active oxygen species, and has a good clinical application value.
2. The preparation method of the sodium metavanadate nanosphere provided by the invention is simple and rapid, does not need special equipment, and has high production efficiency and strong controllability.
Drawings
Fig. 1 shows a transmission electron microscope image of sodium metavanadate nanospheres prepared in example 1.
Fig. 2 shows a transmission electron microscope image of the sodium metavanadate nanosphere prepared in comparative example 1.
Fig. 3 is a schematic diagram showing the signal of the sodium metavanadate nanosphere prepared in example 1 for detecting singlet oxygen by using a paramagnetic resonance spectrometer under different environments.
Fig. 4 is a schematic diagram showing signals of sodium metavanadate nanospheres prepared in example 1 for detecting hydroxyl radicals by using a paramagnetic resonance spectrometer under different environments.
Detailed Description
The present invention is described in detail below by way of examples, it should be noted that the examples are only for the purpose of further illustration, and are not to be construed as limiting the scope of the present invention, and that those skilled in the art can make insubstantial modifications and adaptations to the invention in light of the above teachings. The embodiments and features of the embodiments of the present invention may be combined with each other without conflict. The starting materials and reagents used in the following examples are, unless otherwise specified, commercially available products or can be prepared by known methods.
Example 1
A sodium metavanadate nanosphere is prepared by the following steps:
1) dissolving DSPE-mPEG (mPEG molecular weight is 2000) in chloroform to obtain mixed solution A (concentration is 5 mg/ml);
2) weighing 10mg of sodium metavanadate and dissolving the sodium metavanadate in 2ml of PVA (10mg/ml) aqueous solution to obtain mixed solution B;
3) adding the mixed solution B into 8ml of the mixed solution A, and placing the mixed solution A into an ultrasonic crusher for primary emulsification, wherein the parameters of the ultrasonic crusher are as follows: the size of the amplitude transformer is 6 mm; the power is 300W, the ultrasonic time is 3s, the gap time is 2s, and the process lasts for 3 min; obtaining a primary emulsion;
4) 12ml of PVA aqueous solution (20mg/ml) is added into the primary emulsion, and then the primary emulsion is placed in an ultrasonic crusher for secondary emulsification under the same conditions and time as the primary emulsification. After the secondary emulsification is finished, obtaining secondary emulsion;
5) adding 40ml deionized water into the secondary emulsion, placing in a homogenizing dispersion machine, homogenizing and dispersing at 6000rpm for 0.5h, performing reduced pressure rotary evaporation on the dispersed solution to remove the organic solvent, and performing ultrafiltration, concentration and purification to obtain the final product.
Fig. 1 includes an overall morphology diagram of the sodium metavanadate nanosphere prepared in the embodiment and an enlarged view of a single sodium metavanadate nanosphere, and it can be known that the sodium metavanadate nanosphere prepared in the embodiment is uniformly dispersed spherical particles with an average particle size of about 150-200 nm.
Example 2
A sodium metavanadate nanosphere is prepared by the following steps:
1) dissolving DSPE-mPEG (mPEG molecular weight is 3000) in chloroform to obtain mixed solution A (concentration is 5 mg/ml);
2) weighing 10mg of sodium metavanadate and dissolving the sodium metavanadate in 2ml of PVA (10mg/ml) aqueous solution to obtain mixed solution B;
3) adding the mixed solution B into 8ml of the mixed solution A, and placing the mixed solution A into an ultrasonic crusher for primary emulsification, wherein the parameters of the ultrasonic crusher are as follows: the size of the amplitude transformer is 6 mm; the power is 300W, the ultrasonic time is 3s, the gap time is 2s, and the process lasts for 3 min; obtaining a primary emulsion;
4) 12ml of PVA aqueous solution (20mg/ml) is added into the primary emulsion, and then the primary emulsion is placed in an ultrasonic crusher for secondary emulsification under the same conditions and time as the primary emulsification. After the secondary emulsification is finished, obtaining secondary emulsion;
5) adding 40ml deionized water into the secondary emulsion, placing in a homogenizing dispersion machine, homogenizing and dispersing at 6000rpm for 0.5h, performing reduced pressure rotary evaporation on the dispersed solution to remove the organic solvent, and performing ultrafiltration, concentration and purification to obtain the final product.
The morphology of the sodium metavanadate nanosphere prepared in the embodiment is basically consistent with that of the sodium metavanadate nanosphere prepared in the embodiment 1, the sodium metavanadate nanosphere is uniformly dispersed spherical particles, and the size of the sodium metavanadate nanosphere is about 150-200 nm.
Example 3
A sodium metavanadate nanosphere is prepared by the following steps:
1) weighing 10mg of sodium metavanadate and dissolving the sodium metavanadate in 2ml of PVA (10mg/ml) aqueous solution to obtain mixed solution B;
2) dissolving DSPE-mPEG (mPEG with molecular weight of 5000) in chloroform to obtain mixed solution A (with concentration of 5 mg/ml);
3) adding the mixed solution B into 8ml of the mixed solution A, and placing the mixed solution A into an ultrasonic crusher for primary emulsification, wherein the parameters of the ultrasonic crusher are as follows: the size of the amplitude transformer is 6 mm; the power is 300W, the ultrasonic time is 3s, the gap time is 2s, and the process lasts for 3 min; obtaining a primary emulsion;
4) 12ml of PVA aqueous solution (20mg/ml) is added into the primary emulsion, and then the primary emulsion is placed in an ultrasonic crusher for secondary emulsification under the same conditions and time as the primary emulsification. After the secondary emulsification is finished, obtaining secondary emulsion;
5) adding 40ml deionized water into the secondary emulsion, placing in a homogenizing dispersion machine, homogenizing and dispersing at 6000rpm for 0.5h, performing reduced pressure rotary evaporation on the dispersed solution to remove the organic solvent, and performing ultrafiltration, concentration and purification to obtain the final product.
The morphology of the sodium metavanadate nanosphere prepared in the embodiment is basically consistent with that of the sodium metavanadate nanosphere prepared in the embodiment 1, the sodium metavanadate nanosphere is uniformly dispersed spherical particles, and the size of the sodium metavanadate nanosphere is about 150-200 nm.
Example 4
A sodium metavanadate nanosphere is prepared by the following steps:
1) dissolving FA-DSPE-mPEG (mPEG molecular weight is 2000) in chloroform to obtain mixed solution A (concentration is 5 mg/ml);
2) weighing 10mg of sodium metavanadate and dissolving the sodium metavanadate in 2ml of PVA (10mg/ml) aqueous solution to obtain mixed solution B;
3) adding the mixed solution B into 8ml of the mixed solution A, and placing the mixed solution A into an ultrasonic crusher for primary emulsification, wherein the parameters of the ultrasonic crusher are as follows: the size of the amplitude transformer is 6 mm; the power is 300W, the ultrasonic time is 3s, the gap time is 2s, and the process lasts for 3 min; obtaining a primary emulsion;
4) 12ml of PVA aqueous solution (20mg/ml) is added into the primary emulsion, and then the primary emulsion is placed in an ultrasonic crusher for secondary emulsification under the same conditions and time as the primary emulsification. After the secondary emulsification is finished, obtaining secondary emulsion;
5) adding 40ml deionized water into the secondary emulsion, placing in a homogenizing dispersion machine, homogenizing and dispersing at 6000rpm for 0.5h, performing reduced pressure rotary evaporation on the dispersed solution to remove the organic solvent, and performing ultrafiltration, concentration and purification to obtain the final product.
The morphology of the sodium metavanadate nanosphere prepared in the embodiment is basically consistent with that of the sodium metavanadate nanosphere prepared in the embodiment 1, the sodium metavanadate nanosphere is uniformly dispersed spherical particles, and the size of the sodium metavanadate nanosphere is about 150-200 nm.
Example 6
A sodium metavanadate nanosphere is prepared by the following steps:
1) dissolving mPEG-PLGA (mPEG molecular weight is 5000, and PLGA molecular weight is 5000) in chloroform to obtain mixed solution A (concentration is 5 mg/ml);
2) weighing 10mg of sodium metavanadate and dissolving the sodium metavanadate in 2ml of PVA (10mg/ml) aqueous solution to obtain mixed solution B;
3) adding the mixed solution B into 8ml of the mixed solution A, and placing the mixed solution A into an ultrasonic crusher for primary emulsification, wherein the parameters of the ultrasonic crusher are as follows: the size of the amplitude transformer is 6 mm; the power is 300W, the ultrasonic time is 3s, the gap time is 2s, and the process lasts for 3 min; obtaining a primary emulsion;
4) 12ml of PVA aqueous solution (20mg/ml) is added into the primary emulsion, and then the primary emulsion is placed in an ultrasonic crusher for secondary emulsification under the same conditions and time as the primary emulsification. After the secondary emulsification is finished, obtaining secondary emulsion;
5) adding 40ml deionized water into the secondary emulsion, placing in a homogenizing dispersion machine, homogenizing and dispersing at 6000rpm for 0.5h, performing reduced pressure rotary evaporation on the dispersed solution to remove the organic solvent, and performing ultrafiltration, concentration and purification to obtain the final product.
The morphology of the sodium metavanadate nanosphere prepared in the embodiment is basically consistent with that of the sodium metavanadate nanosphere prepared in the embodiment 1, the sodium metavanadate nanosphere is uniformly dispersed spherical particles, and the size of the sodium metavanadate nanosphere is about 150-200 nm.
Comparative example 1
A sodium metavanadate nanosphere is prepared by the following steps:
1) dissolving mPEG-PLGA (mPEG molecular weight is 5000, and PLGA molecular weight is 5000) in chloroform to obtain mixed solution A (concentration is 10 mg/ml);
2) weighing 10mg of sodium metavanadate and dissolving the sodium metavanadate in 2ml of PVA (10mg/ml) aqueous solution to obtain mixed solution B;
3) adding the mixed solution B into 10ml of the mixed solution A, and placing the mixed solution A into an ultrasonic crusher for primary emulsification, wherein the parameters of the ultrasonic crusher are as follows: the size of the amplitude transformer is 6 mm; the power is 300W, the ultrasonic time is 3s, the gap time is 2s, and the process lasts for 3 min; obtaining a primary emulsion;
4) 12ml of PVA aqueous solution (20mg/ml) is added into the primary emulsion, and then the primary emulsion is placed in an ultrasonic crusher for secondary emulsification under the same conditions and time as the primary emulsification. After the secondary emulsification is finished, obtaining secondary emulsion;
5) adding 40ml deionized water into the secondary emulsion, placing in a homogenizing dispersion machine, homogenizing and dispersing at 6000rpm for 0.5h, performing reduced pressure rotary evaporation on the dispersed solution to remove the organic solvent, and performing ultrafiltration, concentration and purification to obtain the final product.
As can be seen from fig. 2, the present comparative example did not produce the intended sodium metavanadate nanospheres, producing uniformly dispersed nanodots having an average particle size of less than 10 nm. Therefore, if the mass ratio of the amphiphilic polymer of the water oil and the sodium metavanadate is not in the range of the invention, the sodium metavanadate nanosphere consisting of the polymer vesicle and the sodium metavanadate coated by the polymer vesicle can not be prepared at all.
Performance testing
The test method is as follows:
test groups: 100ul of aqueous solution (10mg/ml) of sodium metavanadate nanospheres prepared in the embodiment of the invention is taken, and then the aqueous solution is averagely divided into two groups, one group is added with 10ul of singlet oxygen capture agent TEMP liquid (the purity is not less than 98%) and hydrogen peroxide solution (200 mu M) with the same volume, and a paramagnetic resonance spectrometer is utilized to test singlet oxygen signals; the other group was added with 10ul of a DMPO solution (0.2M) as a radical scavenger and an equal volume of a hydrogen peroxide solution (200. mu.M) and the signals of the hydroxyl radicals were measured using a paramagnetic resonance spectrometer.
Control group: taking 100ul of the aqueous solution of sodium metavanadate nanospheres which is the same as the test group, then evenly dividing the aqueous solution into two groups, adding 10ul of singlet oxygen capture agent TEMP liquid (the purity is larger than or equal to 98%) and deionized water with the same volume into one group, and testing the signal of singlet oxygen by using a paramagnetic resonance spectrometer; the other group was added with 10ul of free radical scavenger DMPO (0.2M) and an equal volume of deionized water and the signal of the hydroxyl radical was measured using paramagnetic resonance spectrometer.
And (3) testing results: as can be seen from fig. 3, the sodium metavanadate nanosphere prepared in example 1 detected a stronger signal of singlet oxygen than that in deionized water under the hydrogen peroxide-rich environment, and thus the sodium metavanadate nanosphere can be used for the chemokinetic treatment.
As can be seen from fig. 4, the sodium metavanadate nanosphere prepared in example 1 has little signal of hydroxyl radical detected in deionized water and strong signal of hydroxyl radical detected in hydrogen peroxide-rich environment, so that the sodium metavanadate nanosphere can be used for chemical kinetic therapy.
The sodium metavanadate nanospheres prepared in examples 2 to 6 were tested in the same manner, and the results were consistent with those of the sodium metavanadate nanosphere of example 1, and all of them were able to react with hydrogen peroxide to generate singlet oxygen and hydroxyl radicals, and thus can be used for chemokinetic treatment.
It should be understood that the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention, and it will be obvious to those skilled in the art that other variations or modifications may be made on the basis of the above description, and all embodiments may not be exhaustive, and all obvious variations or modifications may be made within the scope of the present invention.
Claims (10)
1. The sodium metavanadate nanosphere is characterized by consisting of polymer vesicles and sodium metavanadate coated by the polymer vesicles; the polymersome is formed by water-oil amphiphilic polymer.
2. The sodium metavanadate nanosphere according to claim 1, wherein the average particle size of the sodium metavanadate nanosphere is 100nm to 250 nm.
3. The sodium metavanadate nanosphere of claim 1, wherein said water-oil amphiphilic polymer is an amphiphilic block polymer or an amphiphilic polymer comprising phospholipids and hydrophilic polymer segments; the amphiphilic block polymer consists of a hydrophilic polymer chain segment and a hydrophobic polymer chain segment.
4. The sodium metavanadate nanosphere according to claim 3, wherein when the water-oil amphiphilic polymer is an amphiphilic block polymer, the molecular weight of the hydrophilic polymer segment is 2000-5000, and the molecular weight of the hydrophobic polymer segment is 2000-5000;
when the water-oil amphiphilic polymer is an amphiphilic polymer comprising phospholipid and a hydrophilic polymer segment, the molecular weight of the hydrophilic polymer segment is 2000-5000;
preferably, the amphiphilic polymer comprising phospholipids and hydrophilic polymer segments is selected from distearoylphosphatidylacetamide-polyethylene glycol (DSPE-mPEG) and/or distearoylphosphatidylethanolamine-polyethylene glycol-folic acid (DSPE-mPEG-FA); the amphiphilic block polymer is selected from poly (lactide-co-glycolide) -polyethylene glycol (PLGA-mPEG).
5. A method for preparing sodium metavanadate nanospheres according to any of claims 1 to 4, comprising the following steps:
1) dissolving the water-oil amphiphilic polymer in an organic solvent to obtain a mixed solution A;
2) dissolving sodium metavanadate in a polyvinyl alcohol aqueous solution to obtain a mixed solution B;
3) mixing the mixed solution A and the mixed solution B, and carrying out primary emulsification to obtain primary emulsion;
4) adding the primary emulsion into a polyvinyl alcohol aqueous solution for secondary emulsification to obtain a secondary emulsion;
5) homogenizing the secondary emulsion, removing organic solvent, and concentrating.
6. The preparation method according to claim 5, wherein the mass ratio of the water-oil amphiphilic polymer to the sodium metavanadate is 7-9: 2;
preferably, in step 3), the volume ratio of the mixed solution B to the mixed solution a is 1: 4-5.
7. The method according to claim 5, wherein the organic solvent is dichloromethane or chloroform in step 1).
8. The method according to claim 5, wherein in the step 2), the solubility of the aqueous solution of polyvinyl alcohol is 1mg/ml to 10 mg/ml;
preferably, in the step 4), the solubility of the polyvinyl alcohol aqueous solution is 2mg/ml-20 mg/ml.
9. The method for preparing according to claim 5, wherein the first emulsification and the second emulsification are performed in a sonicator;
preferably, the parameters of the ultrasonicator are as follows: the size of the amplitude transformer is 6-10 mm; the power is 200-400W; the ultrasonic time is 1-3s, and the gap time is 1-2 s.
10. Use of sodium metavanadate nanospheres according to any one of claims 1 to 4 or prepared according to the preparation method of any one of claims 5 to 9 for the preparation of a chemokinetic therapeutic drug or reagent;
preferably, the sodium metavanadate nanosphere is applied to preparation of a drug or a reagent for treating tumor through chemokinetics.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1140997A (en) * | 1994-01-18 | 1997-01-22 | 西奈山医院公司 | Vanadate compounds for the treatment of proliferative disorders metastases and drug resistant tumors |
| US5871779A (en) * | 1994-01-18 | 1999-02-16 | Mount Sinai Hospital Corporation | Treatment of arthropathies with vanadate compounds or analogues thereof |
| US20030235619A1 (en) * | 2001-12-21 | 2003-12-25 | Christine Allen | Polymer-lipid delivery vehicles |
| CN102083878A (en) * | 2008-05-13 | 2011-06-01 | 华盛顿大学 | Diblock copolymers and polynucleotide complexes thereof for delivery into cells |
| CN103422111A (en) * | 2012-05-15 | 2013-12-04 | 攀钢集团攀枝花钢钒有限公司 | Preparing method for sodium metavanadate |
| CN104724756A (en) * | 2013-12-23 | 2015-06-24 | 中国科学院上海硅酸盐研究所 | Method for preparing controllable-size specific-structure vanadium oxide by one-step process |
| CN107847505A (en) * | 2014-09-11 | 2018-03-27 | 威登卓制药公司 | Multilayer lipid vesicle composition and application method |
-
2021
- 2021-04-06 CN CN202110366172.0A patent/CN113087017A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1140997A (en) * | 1994-01-18 | 1997-01-22 | 西奈山医院公司 | Vanadate compounds for the treatment of proliferative disorders metastases and drug resistant tumors |
| US5871779A (en) * | 1994-01-18 | 1999-02-16 | Mount Sinai Hospital Corporation | Treatment of arthropathies with vanadate compounds or analogues thereof |
| US20030235619A1 (en) * | 2001-12-21 | 2003-12-25 | Christine Allen | Polymer-lipid delivery vehicles |
| CN102083878A (en) * | 2008-05-13 | 2011-06-01 | 华盛顿大学 | Diblock copolymers and polynucleotide complexes thereof for delivery into cells |
| CN103422111A (en) * | 2012-05-15 | 2013-12-04 | 攀钢集团攀枝花钢钒有限公司 | Preparing method for sodium metavanadate |
| CN104724756A (en) * | 2013-12-23 | 2015-06-24 | 中国科学院上海硅酸盐研究所 | Method for preparing controllable-size specific-structure vanadium oxide by one-step process |
| CN107847505A (en) * | 2014-09-11 | 2018-03-27 | 威登卓制药公司 | Multilayer lipid vesicle composition and application method |
Non-Patent Citations (1)
| Title |
|---|
| 孟丹 等: "聚合物脂质纳米球的制备优化", 《现代生物医学进展》 * |
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